The overall objective of the proposed research is to develop molecular therapies for pseudoxanthoma elasticum (PXE), a pleiotropic multisystem disorder affecting the skin, the eyes, and the cardiovascular system with progressive pathological mineralization of soft connective tissues, primarily the elastic structures. This heritable disease is caused by mutations in the ABCC6 gene, which is highly expressed in the liver and the kidneys and serves as a metabolic transmembrane transporter. The metabolic nature of PXE has been proven by our recent studies using a PXE mouse grafting and parabiosis models (see Preliminary Studies). However, there is no cure or effective treatment for PXE so far.